Rare Angioinvasive Fungal Infection in Association With Leukemia Cutis
Leukemia cutis (LC) is characterized by the infiltration of malignant neoplastic leukocytes or their precursors into the skin and is most often seen in conjunction with systemic leukemia. Patients with LC frequently are in a relative or absolute immunocompromised state. We report the case of a 52-year-old man with primary refractory acute myelogenous leukemia (AML) following allogeneic stem cell transplant (SCT) who presented with a progressive reddish purple nodule with surrounding erythema and central necrosis in the setting of leukocytosis and possible fungal pneumonia. Histopathologic examination revealed an ulcerated dense diffuse dermal infiltrate of large atypical lymphocytes consistent with LC and septate hyphae with acute-angle branching in the dermal blood vessels. Cultures from a biopsied lesion grew Paecilomyces species, a rare but emerging opportunistic infection, despite the patient being on antifungal prophylaxis. This novel report of a rare angioinvasive infection occurring within a lesion of LC supports the need to maintain a high index of suspicion for invasive infection in patients with hematologic malignancy, even those on antifungal prophylaxis.
Practice Points
- Immunosuppressed patients are at risk for atypical presentations of common infections as well as infection with rare pathogens.
- Skin biopsy and tissue culture play an important role in identifying infectious agents in immunosuppressed patients.
- Leukemic infiltrates may mask pathogens, and pathologists should strongly consider additional stains when indicated.
Leukemia cutis has a wide range of cutaneous manifestations and may present with solitary or multiple papular, nodular, or plaquelike lesions that are red-brown, blue, violaceous, or hemorrhagic.4 Leukemia cutis occurs most commonly on the legs, followed by the arms, back, chest, scalp, and face.2,4 Leukemia cutis may be hard to distinguish clinically from other conditions such as cutaneous metastases of visceral malignancies, lymphoma, drug eruptions, and opportunistic infections. Leukemia cutis ulcers often measure only a few centimeters in diameter with a firmly adherent purulent or hemorrhagic crust and may occur in unusual locations. These lesions usually are treatment resistant and their persistence may help to lead to diagnosis.4
Microscopically, most LC lesions show a perivascular or periadnexal pattern of involvement or a dense diffuse, interstitial, or nodular atypical lymphocytic infiltrate involving the dermis and subcutis with sparing of the upper papillary dermis.2 The cytologic appearance of M1 and M2 subtypes of AML are characterized by medium-sized to large mononuclear cells with a light cytoplasm and large basophilic cell nuclei. The M4 and M5 subtypes of AML generally are dominated by medium-sized, round or oval-shaped mononuclear cells that may have eosinophilic cytoplasm and segmented or kidney-shaped basophilic nuclei.4 Immunophenotyping is crucial for diagnosis. In myeloid disorders, there is positive staining with markers of myeloid lineage such as myeloperoxidase, lysozyme, CD34, CD15, CD68, CD43, and CD117.5
In our patient, there was an ulcerated dense diffuse dermal infiltrate of large atypical lymphocytes consistent with LC and positive immunostaining consistent with LC associated with AML. Additionally, septate hyphae with acute-angle branching also were noted in the dermal blood vessels on hematoxylin and eosin and fungal staining, demonstrating concomitant fungal infection. Angioinvasion of organisms demonstrated on skin biopsy and persistent pneumonia noted on chest imaging suggested a disseminated infectious process.
Invasive fungal infections are an increasing cause of morbidity and mortality in immunocompromised individuals, including those with hematologic malignancies and hematologic SCTs. Despite an increasing number of antifungal therapies, outcomes are frequently suboptimal with mortality rates often greater than 50% depending on the pathogen and disease.6 Thus, there must be a high index of suspicion of infection even when a separate histopathologic diagnosis is available, such as the finding of leukemic infiltrates in this patient’s biopsy specimen. A similar case of LC has been reported with concomitant fungal infection involving Fusarium and Enterococcus.7 Patients with leukemic cells may develop leukemic infiltrates in response to cutaneous infection, and a high index of suspicion for 2 related but distinct processes is necessary.
Paecilomyces species are an emerging cause of opportunistic and usually severe human infections.8-11 The Paecilomyces species are saprophytic filamentous fungi that are found worldwide in soil as well as contaminants in the air and water.12Paecilomyces infection is generally associated with the use of immunosuppressive therapies, implants, or ocular surgery. Among species in this genus, Paecilomyces lilacinus and Paecilomyces variotii are of clinical importance. Most species have high susceptibility to the newer azoles such as voriconazole.6
Conclusion
Despite continued treatment with voriconazole, our patient still developed a rare fungal infection arising in a lesion of LC. He had signs of infection, including an elevated white blood cell count, fever, and malaise, which are nonspecific clinical findings that could have been attributed to known relapse of systemic leukemia or to known enterococcemia. Even in patients on antifungal prophylaxis and with other possible causes of leukocytosis, this case illustrates that there must be a high index of suspicion for angioinvasive fungal infection.
